Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System
The hypothesis behind the proposed trial of surfactant therapy for COVID-19 infected patients requiring ventilator support is that endogenous surfactant is dysfunctional. This could be due to decreased concentration of surfactant phospholipid and protein, altered surfactant phospholipid composition, surfactant protein proteolysis and/or oedema protein inhibition of surfactant surface tension function and/or oxidative inactivation of surfactant proteins. Variations of these dysfunctional mechanisms have been reported in a range of lung diseases, including cystic fibrosis and severe asthma, and in child and adult patients with ARDS. Our studies of surfactant metabolism in adult ARDS patients showed altered percentage composition of surfactant PC, with decreased DPPC and increased surface tension-inactive unsaturated species, and decreased concentrations of both total PC and phosphatidylglycerol (PG) The SARS-CoV-2 virus binds to the angiotensin converting enzyme-2 (ACE2) receptor, which is preferentially expressed in the peripheral lung ATII cells. Consequent viral infection of ATII cells could reduce cell number and impair the capacity of the lungs to synthesise and secrete surfactant. This, however, has not yet been demonstrated empirically in COVID-19 patients. If this is the case, then exogenous surfactant administration to the lungs is potential one treatment option to mitigate disease severity in these patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Device introduces surfactant to the patients lungs
Standard of care treatment for respiratory illness
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Oxygenation Improvement
To assess the improvement in oxygenation as determined by the PaO2/FiO2 ratio after treatment with study treatment
Time frame: 3 months
Pulmonary ventilation Improvement
To assess the improvement in pulmonary ventilation as determined by the Ventilation Index (VI), where VI = (Respiratory rate X PIP X PaCo2 (mmHg)/ 1000 after study treatment.
Time frame: 3 months
IMV Need
Need for invasive mechanical ventilation (IMV) (CPAP/NIV arm only)
Time frame: 3 months
Safety Assessment of Frequency and Severity of Adverse Events
To assess safety as judged by the frequency and severity of adverse events and severe adverse events (SAEs).
Time frame: 3 months
Change in PaO2/FiO2 ratio
Mean change in PaO2/FiO2 ratio at 24 and 48 hours after study initiation.
Time frame: 3 months
Mean Change in ventilatory index
Mean change in ventilatory index (VI) at 24 and 48 hours after study initiation
Time frame: 48 hours
Mean Change in pulmonary compliance
Mean change in pulmonary compliance (L/cmH2O) at 24 and 48 hours after study initiation in the IMV arm
Time frame: 48 hours
Mean Change in PEEP requirement
Mean change in PEEP (Positive End-Expiratory Pressure) requirement at 24 and 48 hours after study initiation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 48 Hours
Clinical Improvement
To evaluate clinical improvement defined by time to one improvement point on an ordinal scale, as described in the WHO master protocol (2020) daily while hospitalised and on days 15 and 28
Time frame: 28 days
Mechanical ventilation duration
Duration of mechanical ventilation
Time frame: 3 months
Duration of days
Duration of days of IMV or NIV or CPAP
Time frame: 3 months
IMV free days
Invasive Mechanical Ventilator (IMV) free days at day 21
Time frame: 21 days
Ventilator support free days
Ventilator support (IMV or NIV or CPAP) free days (VSFD) at day 21
Time frame: 21 days
Length of ICU stay
Length of intensive care unit stay
Time frame: 3 months
Number of days hospitalised
Number of days hospitalised
Time frame: 3 months
Mortality
Mortality at day 28
Time frame: 28 days